ArticleCell death & disease2014
Transcriptional and metabolic adaptation of human neurons to the mitochondrial toxicant MPP(+).
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 105 citations in OpenAlex.
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- Definition of the Neurotoxicity-Associated Metabolic Signature Triggered by Berberine and Other Respiratory Chain Inhibitors.Antioxidants (Basel, Switzerland) · 2023Article
- Identification of the bacterial metabolite aerugine as potential trigger of human dopaminergic neurodegeneration.Environment international · 2023Article
- Prolonged Differentiation of Neuron-Astrocyte Co-Cultures Results in Emergence of Dopaminergic Neurons.International journal of molecular sciences · 2023Article
- Dynamic Metabolic and Transcriptional Responses of Proteasome-Inhibited Neurons.Antioxidants (Basel, Switzerland) · 2023Article
- Human IPSC 3D brain model as a tool to study chemical-induced dopaminergic neuronal toxicity.Neurobiology of disease · 2022Article
- Mapping the cellular response to electron transport chain inhibitors reveals selective signaling networks triggered by mitochondrial perturbation.Archives of toxicology · 2022Article
- Acute effects of the imidacloprid metabolite desnitro-imidacloprid on human nACh receptors relevant for neuronal signaling.Archives of toxicology · 2021Article
- Small Molecule Fisetin Modulates Alpha-Synuclein Aggregation.Molecules (Basel, Switzerland) · 2021Article
- Functional alterations by a subgroup of neonicotinoid pesticides in human dopaminergic neurons.Archives of toxicology · 2021Article
- Metabolic Targets of Coenzyme Q10 in Mitochondria.Antioxidants (Basel, Switzerland) · 2021Review
- C9orf72 regulates energy homeostasis by stabilizing mitochondrial complex I assembly.Cell metabolism · 2021Article
- Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors.Archives of toxicology · 2021Article
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 4 countries.
Funding
Abstract
Assessment of the network of toxicity pathways by Omics technologies and bioinformatic data processing paves the road toward a new toxicology for the twenty-first century. Especially, the upstream network of responses, taking place in toxicant-treated cells before a point of no return is reached, is still little explored. We studied the effects of the model neurotoxicant 1-methyl-4-phenylpyridinium (MPP(+)) by a combined metabolomics (mass spectrometry) and transcriptomics (microarrays and deep sequencing) approach to provide unbiased data on earliest cellular adaptations to stress. Neural precursor cells (LUHMES) were differentiated to homogeneous cultures of fully postmitotic human dopaminergic neurons, and then exposed to the mitochondrial respiratory chain inhibitor MPP(+) (5 μM). At 18-24 h after treatment, intracellular ATP and mitochondrial integrity were still close to control levels, but pronounced transcriptome and metabolome changes were seen. Data on altered glucose flux, depletion of phosphocreatine and oxidative stress (e.g., methionine sulfoxide formation) confirmed the validity of the approach. New findings were related to nuclear paraspeckle depletion, as well as an early activation of branches of the transsulfuration pathway to increase glutathione. Bioinformatic analysis of our data identified the transcription factor ATF-4 as an upstream regulator of early responses. Findings on this signaling pathway and on adaptive increases of glutathione production were confirmed biochemically. Metabolic and transcriptional profiling contributed complementary information on multiple primary and secondary changes that contribute to the cellular response to MPP(+). Thus, combined 'Omics' analysis is a new unbiased approach to unravel earliest metabolic changes, whose balance decides on the final cell fate.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.